Inhibition of β-catenin–TCF1 interaction delays differentiation of mouse embryonic stem cells

Chatterjee, Satabdi; Saj, Abil; Gocha, Tenzin; Murphy, Matthew; Gonsalves, Foster C.; Zhang, Xiaoqian; Hayward, Penelope; Oksuz, Betül Akgöl; Shen, Steven S.; Madar, Aviv; Arias, Alfonso Martínez; DasGupta, Ramanuj

doi:10.1084/jem.21211oia90

Cited by 5 publications

(5 citation statements)

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“…A cut-off of twofold was used to allocate transcripts as either RA-enriched (420 transcripts) or LIF-enriched (28 transcripts). We mined publicly available transcriptome data [65] and classified transcripts that were more than twofold upregulated after RA treatment as "differentiation-responsive genes" and more than twofold downregulated as "pluripotency-associated genes". Genes that showed tsRNA/Scr1 was > 2-fold in both the LIF and RA conditions and similar enrichments in both the conditions were categorized as "Ubiquitous".…”

Section: Tsrna-mediated Mrna Pulldown Library and Analysismentioning

confidence: 99%

Dynamic expression of tRNA‐derived small RNAs define cellular states

et al. 2019

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Transfer RNA (tRNA)‐derived small RNAs (tsRNAs) have recently emerged as important regulators of protein translation and shown to have diverse biological functions. However, the underlying cellular and molecular mechanisms of tsRNA function in the context of dynamic cell‐state transitions remain unclear. Expression analysis of tsRNAs in distinct heterologous cell and tissue models of stem vs. differentiated states revealed a differentiation‐dependent enrichment of 5′‐tsRNAs. We report the identification of a set of 5′‐tsRNAs that is upregulated in differentiating mouse embryonic stem cells (mESCs). Notably, interactome studies with differentially enriched 5′‐tsRNAs revealed a switch in their association with “effector” RNPs and “target” mRNAs in different cell states. We demonstrate that specific 5′‐tsRNAs can preferentially interact with the RNA‐binding protein, Igf2bp1, in the RA‐induced differentiated state. This association influences the transcript stability and thereby translation of the pluripotency‐promoting factor, c‐Myc, thus providing a mechanistic basis for how 5′‐tsRNAs can modulate stem cell states in mESCs. Together our study highlights the role of 5′‐tsRNAs in defining distinct cell states.

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Section: Tsrna-mediated Mrna Pulldown Library and Analysismentioning

confidence: 99%

Dynamic expression of tRNA‐derived small RNAs define cellular states

et al. 2019

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“…In the active state, unphosphorylated β-catenin accumulates in the cytoplasm and translocates into the nucleus, acting as a central effector of the canonical Wnt signaling cascade (Wodarz and Nusse 1998). The β-catenin and nuclear transcription factor lymphoid enhancer factor/T cell factor (LEF/TCF) complex (Arce and others 2006; Bem and others 2019; Chatterjee and others 2015) determines cell proliferation and differentiation by activating a series of Wnt signaling target genes (Chatterjee and others 2015; Kalani and others 2008). Notably, the transcriptional response system responds to fold changes but not absolute levels of β-catenin (Goentoro and Kirschner 2009).…”

Section: Overview Of Wnt/β-catenin Signalingmentioning

confidence: 99%

Wnt/β-Catenin Signaling in Neural Stem Cell Homeostasis and Neurological Diseases

et al. 2020

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Neural stem/progenitor cells (NSCs) maintain the ability of self-renewal and differentiation and compose the complex nervous system. Wnt signaling is thought to control the balance of NSC proliferation and differentiation via the transcriptional coactivator β-catenin during brain development and adult tissue homeostasis. Disruption of Wnt signaling may result in developmental defects and neurological diseases. Here, we summarize recent findings of the roles of Wnt/β-catenin signaling components in NSC homeostasis for the regulation of functional brain circuits. We also suggest that the potential role of Wnt/β-catenin signaling might lead to new therapeutic strategies for neurological diseases, including, but not limited to, spinal cord injury, Alzheimer’s disease, Parkinson’s disease, and depression.

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“…Depending on the signals provided, ESCs can differentiate into a variety of cell types (Wobus and Boheler, 2005). LIF/ STAT3, WNT/b-catenin, and bone morphogenetic protein (BMP)/SMAD have been suggested as context-dependent regulators of both ESC self-renewal and differentiation (Chatterjee et al, 2015;Funa et al, 2015;Itoh et al, 2014;Niwa et al, 1998;Zhang et al, 2013). In contrast, retinoic acid (RA) is known as an efficient inducer of ESC differentiation (Gudas and Wagner, 2011;Rochette-Egly, 2015;Simandi et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation

et al. 2016

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Cell type specification relies on the capacity of undifferentiated cells to properly respond to specific differentiation-inducing signals. Using genomic approaches along with loss- and gain-of-function genetic models, we identified OCT4-dependent mechanisms that provide embryonic stem cells with the means to customize their response to external cues. OCT4 binds a large set of low-accessible genomic regions. At these sites, OCT4 is required for proper enhancer and gene activation by recruiting co-regulators and RAR:RXR or β-catenin, suggesting an unexpected collaboration between the lineage-determining transcription factor and these differentiation-initiating, signal-dependent transcription factors. As a proof of concept, we demonstrate that overexpression of OCT4 in a kidney cell line is sufficient for signal-dependent activation of otherwise unresponsive genes in these cells. Our results uncover OCT4 as an integral and necessary component of signal-regulated transcriptional processes required for tissue-specific responses.

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Inhibition of β-catenin–TCF1 interaction delays differentiation of mouse embryonic stem cells

Cited by 5 publications

References 1 publication

Dynamic expression of tRNA‐derived small RNAs define cellular states

Dynamic expression of tRNA‐derived small RNAs define cellular states

Wnt/β-Catenin Signaling in Neural Stem Cell Homeostasis and Neurological Diseases

OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation

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